The acquired immunodeficiency syndrome (AIDS) has become a global pandemic with over 366,000 cases reported from 162 counthes. A major focus within our unit has been defining the unique epidemiologic, clinical, virologic and immunologic features of human immunodeficiency virus type 1 (HIV-1) infection in Africa and other tropical countries. In two related studies in Kinshasa, Zaire we demonstrated that AIDS is the leading cause of death with HIV seroprevalence in 43% of adult deaths. We also demonstrated that 40% of 1200 female prostitutes in Kinshasa and 14% of 546 Nigerian prostitutes were HIV-1 seropositive, and that incident infections (3%/yr) were strongly correlated with genital ulcers and chlamydial infections. In studies of perinatal infection, in over 600 children born to HIV infected mothers in Zaire and Haiti, we documented a 28% transmission rate of HIV-1 infection and a cumulative mortality rate of 70% in the first two years of life. Of surviving children during the first year of life a beneficial effect of immunizations against commonly occuring childhood infectious diseases was observed despite the lower immunogenicity in HIV-1 seropositive individuals. In virologic studies we demonstrated that no single diagnostic assay was reliable in diagnosing perinatally acquired HIV infection within the first month of life, but that by 3 months, HIV culture, polymerase chain reaction and lgA each had a high positive predictive value which further improved at 6 and 9 months of age. Additional studies demonstrated the presence of neutralizing antibody to the V3 loop region of HIV-1mn in HIV-infected individuals in the U.S., Zaire and Brazil, but we were unable to document an association between the presence of these neutralizing antibodies and decreased perinatal transmission rates. In contrast, perinatal transmission was independently associated with decreased number of CD4 cells and chorioamnionitis. Additional virologic and immunologic studies further defined the prognostic importance of p24 antigenemia following acid hydrolysis, the role of cytokines, particularly TNF-alpha, and activated T-cell subsets in the natural history and immunopathogenesis of HIV infection. Further studies will continue to examine virologic and immunologic aspects of human retroviral infections internationally.